PHASE II EFFICACY OF HUMAN MONOCLONAL ANTIBODY TREATMENT TO PREVENT C. DIFFICILE RECURRENCE

June 2, 2009

JAMAICA PLAIN, Mass., -- The use of two different monoclonal antibodies, CDA1 and CDB1, administered together along with standard of care antibiotics, reduces the risk of recurrence of C. difficile diarrhea, according to results of a study presented by researchers from MassBiologics of the University of Massachusetts Medical School and Medarex, Inc. (Princeton, NJ). Of note, the treatment showed efficacy for the BI/Nap1/027 epidemic strain as well as for those with multiple prior episodes of C. difficile diarrhea. Results also suggest an effect in reducing the severity of infection of the first episode of disease, and reduction of additional hospitalizations although further study will be needed to confirm these results. The combination was well tolerated with a good safety profile.

 Recurrence of C. difficile is a major medical problem with the emergence of an epidemic hypervirulent strain and estimates of the disease occurrence keep climbing. Patients who experience one recurrence have a 25 percent chance of a second episode and patients having more than one episode of C. difficile diarrhea have up to a 60 percent chance of recurrence.

 “C. difficile diarrhea is a world-wide epidemic that is on the rise,” said Donna Ambrosino, MD, executive director of MassBiologics and senior investigator of the study. “We need new approaches to prevent the recurrence of C. difficile to decrease morbidity, hospitalizations and health utilization costs.”

 This randomized, double-blind, placebo-controlled phase II study examined attacking the problem of C. difficile differently, as an antibody approach that has never been previously examined. Earlier approaches have included the use of antibacterials/antibiotics or “tying up” the toxins upon exposure.

 In this study, 200 patients from 30 clinical sites received either CDA1+CDB1 (101 patients) or placebo (99 patients) in addition to standard of care antibiotics. Treatment with CDA1+CDB1 resulted in a 70 percent reduction in recurrence rate in a complete intent to treat analysis. Of those who received CDA1+CDB1 treatment for the initial episode of C. difficile, 29.7 percent experienced severe diarrhea compared to 43.4 percent of those in the placebo group. Duration of initial hospitalization for patients was unaffected by CDA1+CDB1 (9.5 vs. 9.4 days), however exploratory analysis found that the affected proportion of patients who were subsequently hospitalized after infusion was significantly reduced (8.9 percent vs. 20 percent). All adverse events that reached significance were experienced by patients on the placebo arm, such as dehydration (0 percent vs. 5 percent) and low blood pressure (0 percent vs. 7 percent).

 The study was funded by MassBiologics of the University of Massachusetts Medical School, and Medarex, Inc., who are equal partners in developing the product.

Dr. Israel Lowy, from Medarex, will present this study on Tuesday, June 2 at 2:15 p.m. Central Time in Room E451B, McCormick Place.

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